Efficacy and Safety of Tinengotinib Tablets Combined With Fulvestrant Injection in Patients With HR Positive and HER-2 Negative Recurrent or Metastatic Breast Cancer Who Have Failed Prior Treatment

A Phase II, Open-Label, Multicenter Clinical Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of TT-00420 (Tinengotinib) Tablets Combined With Fulvestrant Injection in Patients With Hormone Receptor-Positive (HR+) and Human Epidermal Growth Factor Receptor 2 (HER-2) Negative or Low-Expressing Recurrent or Metastatic Breast Cancer Who Have Failed Prior Treatment

The goal of this clinical trial is to learn if tinengotinib combined with fulvestrant works to treat patients with HR-Positive and HER-2-Negative or low-expressing advanced breast cancer. It will also learn about the safety of combination therapy. The main questions it aims to answer are:

1. Does tinengotinib combined with fulvestrant reduce the tumor burden in participants?
2. What medical problems do participants have when taking the combination therapy?

Participants will:

Take tinengotinib and fulvestrant to find the optimal dose of tinengotinib for the combination therapy in Part A.

In Part B, will take tinengotinib at the optimal dose with fulvestrant or tinengotinib alone to see if the combination therapy works better than tinengotinib monotherapy.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Tinengotinib at the optimal dose combined with Fulvestrant; Drug: Tinengotinib; Drug: tinengotinib combined with fulvestrant

• Study Type: Interventional
• Enrollment (Estimated): 94
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Caixia Sun; Phone Number: 025-58216298; Email: sun_caixia@transtherabio.com

Study Locations

• China
  • Beijing, China, 100021
    • Recruiting
    • Cancer hospital, Chinese Academy of Medical Sciences
    • Contact: Binghe Xu, MD
  • Beijing, China
    • Not yet recruiting
    • Beijing Cancer Hospital
    • Contact: Huiping Li, MD
  • Beijing, China
    • Not yet recruiting
    • The First Medical Center, Chinese PLA General Hospital
    • Contact: Weihong Zhao, MD
  • Chongqing, China
    • Not yet recruiting
    • Southwest Hospital
    • Contact: Yi Zhang, MD
  • Shanghai, China
    • Not yet recruiting
    • Fudan University Shanghai Cancer Center
    • Contact: Hongxia Wang, MD
  • Tianjin, China
    • Not yet recruiting
    • Tianjin Medical University Cancer Institute & Hospital
    • Contact: Zhongsheng Tong, MD
  • Guangdong
    • Guangzhou, Guangdong, China
      • Not yet recruiting
      • Guangdong Provincial People's Hospital
      • Contact: Kun Wang, MD
  • Hubei
    • Wuhan, Hubei, China
      • Not yet recruiting
      • Zhongnan Hospital of Wuhan University
      • Contact: Haijun Yu, MD
  • Hunan
    • Changsha, Hunan, China
      • Not yet recruiting
      • Hunan Cancer Hospital
      • Contact: Quchang Ouyang, MD
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Not yet recruiting
      • Jiangsu Province Hospital
      • Contact: Yongmei Yin, MD
  • Shandong
    • Jinan, Shandong, China
      • Not yet recruiting
      • Shandong Cancer Hospital
      • Contact: Huihui Li, MD
    • Linyi, Shandong, China
      • Recruiting
      • LinYi Cancer Hospital
      • Contact: Guozhu Liu, MD
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Not yet recruiting
      • Zhejiang Cancer Hospital
      • Contact: Hai Hu, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically or cytologically confirmed breast cancer with evidence of local recurrence or distant metastasis and no indication for surgery or radiotherapy;
2. Breast cancer confirmed as HR+/HER2- negative or low expression by local laboratory testing based on the most recent tumor tissue sample (from either the primary or metastatic site, excluding bone lesions). HR-positive, HER2-negative or low expression as defined in this study refer to the Chinese Society of Clinical Oncology [CSCO] 2024 criteria;
3. Participants must meet at least one of the following criteria: a) prior bilateral oophorectomy, or age ≥60 years; b) age <60 years, with natural amenorrhea (in the absence of medication or pathological conditions) for ≥12 months, and estradiol and FSH levels within the postmenopausal range; c) age <60 years, currently undergoing ovarian suppression therapy (e.g., LHRH agonist) and requiring continued treatment during the study, with estradiol and FSH levels maintained within the postmenopausal range;
4. Participants who have previously failed 1-2 lines of endocrine therapy (including AI, SERD, and SERM) for recurrent or metastatic disease are eligible. Subjects with initial diagnosis showing weak ER positivity by IHC (tumor cells with nuclear staining accounting for 1%-10%) are not eligible for enrollment;
5. Participants must have experienced disease progression after prior treatment with at least one CDK4/6 inhibitor (CDK4/6i), including in the neoadjuvant, adjuvant, or systemic treatment settings;
6. Participants who have previously failed 0-2 lines of systemic chemotherapy (cytotoxic drugs) for recurrent or metastatic disease. Antibody-drug conjugates (ADCs) are not counted as systemic chemotherapy;
7. ECOG ≤ 1;
8. Participants must meet at least one of the following criteria (per RECIST v1.1): a) At least one measurable lesion as defined by RECIST v1.1 at baseline; if the only target lesion is a non-nodal lesion, its longest diameter must be ≥15 mm; b) When bone lesions are the only measurable lesions, lytic or mixed bone lesions may be selected as target lesions; subjects with only blastic bone lesions are not eligible for enrollment.
9. Adequate organ and bone marrow function;
10. Premenopausal participants receiving ovarian suppression therapy must agree to use adequate contraception to avoid pregnancy during the study and for at least 3 months after the end of treatment;
11. Able to sign informed consent and comply with the protocol.

Exclusion Criteria:

1. Participants who are pregnant or breastfeeding;
2. Conditions judged by the investigator as making the participant unsuitable for study drug treatment, including but not limited to: a history of severe allergy to the components or excipients of the study drug, prior treatment history with the study drug, or presence of complications that may be life-threatening in the short term (such as pleural, pericardial, or abdominopelvic effusions that cannot be controlled by drainage or other methods);
3. Uncontrolled hypertension (systolic blood pressure >150 mmHg or diastolic blood pressure >100 mmHg), allowing for the lowest value from up to two repeat measurements;
4. Participants with brain or central nervous system (CNS) metastases that have progressed as confirmed by imaging or clinically within 28 days before the start of treatment (e.g., evidence of new or enlarging brain metastases on imaging, new neurological symptoms attributable to brain/CNS metastases);
5. Participants with concurrent other malignancies or hematologic malignancies that are progressing or require active treatment (excluding basal cell carcinoma of the skin, other non-invasive or indolent malignancies, or cured tumors); Hormone replacement therapy is permitted (e.g., thyroxine replacement therapy post-thyroidectomy);
6. Participants who have received systemic treatment with corticosteroids (>10 mg/day of prednisone or equivalent dose of other corticosteroids) or other immunosuppressive medications within 14 days prior to the initiation of the study drug;
7. Participants who have received other systemic anti-tumor therapies or treatment with investigational drugs prior to the initiation of the study drug, with a washout period of approximately 5 half-lives or 14 days, whichever is shorter;
8. Participants who have received extensive radiotherapy or major surgery within 4 weeks prior to the initiation of the study drug, or local palliative radiotherapy within 2 weeks. (If the investigator judges that this does not pose an additional safety risk, initiation of the study drug during the washout period may be permitted with sponsor agreement.)
9. Participants who have not yet recovered from adverse events resulting from prior anti-tumor therapy (excluding adverse events ≤ Grade 1 per CTCAE, or ≤ Grade 2 adverse events that the investigator judges do not pose a safety risk).
10. History of severe cardiac or cerebrovascular disease;
11. Participants who have severe gastrointestinal disease or gastrointestinal dysfunction that may lead to absorption, metabolism or excretion of the study drug, enrollment eligibility will be based on the investigator's judgment (including but not limited to total gastrotomy, short bowel syndrome).
12. Participants who have bleeding disorders or thrombotic disorders or therapeutic anticoagulant therapy requiring INR monitoring.
13. Participants who have received a strong CYP3A inhibitor and inducer before starting the study drug, within an interval of ≤ 2 weeks or 5 half-lives (whichever is shorter);
14. Tested positive for the human immunodeficiency virus (HIV);
15. Participants with active HBV infection and/or HCV infection;
16. Participants who are unable to swallow or tolerate oral medication.
17. The investigator determines that there are other reasons making the participant unsuitable for participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part B (combination therapy)	Drug: Tinengotinib at the optimal dose combined with Fulvestrant; Participants will receive tinengotinib at the optimal dose once daily with fulvestrant in 28-day cycles per protocol defined schedule.
Experimental: Part B (monotherapy therapy)	Drug: Tinengotinib; Participants will receive tinengotinib once daily in 28-day cycles per protocol defined schedule.
Experimental: Part A (dose optimization)	Drug: tinengotinib combined with fulvestrant; Participants will take tinengotinib at the starting dose of 10 mg once daily with fulvestrant to determine the optimal dose of tinengotinib in combination with fulvestrant. If not tolerated, the dose of tinengotinib will be reduced to 8 mg or 6 mg once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: safety evaluation parameters	Including incidence, duration, and severity of DLTs and treatment-related adverse events (TRAEs)	From signing of the informed consent until 28 days after the last dose or the end of the study (whichever occurs first), an average of 1 year.
Part B: Objective Response Rate (ORR) (RECIST v1.1)	The proportion of subjects who achieved a complete response (CR) or a partial response (PR) based on RECIST version 1.1.	From first study drug administration to the end of treatment, an average of 1 year.

Collaborators and Investigators

• Sponsor: TransThera Sciences (Nanjing), Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 17, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: March 19, 2026
• First Submitted That Met QC Criteria: March 25, 2026
• First Posted (Actual): March 27, 2026

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 25, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Estradiol; Estrenes; Estranes; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Fulvestrant
• Other Study ID Numbers: TT00420CN15

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No